Abstract: Disclosed herein are antibiotic compositions, for example compositions that comprise a metal-containing agent and an organoselenium agent, and uses thereof.
Abstract: A method for treating a prokaryotic infection in an animal or human by administering a pharmaceutically acceptable composition, comprising administering a source of silver ions and a benzoisoselenazol derivative, e.g., an ebselen derivative.
Abstract: A method for treating a prokaryotic infection in an animal or human by administering a pharmaceutically acceptable composition, comprising administering a source of silver ions and a benzoisoselenazol derivative, e.g., an ebselen derivative.
Abstract: The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with Ki of 0.14 ?M and 0.46 ?M, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains.
Type:
Grant
Filed:
March 23, 2011
Date of Patent:
November 26, 2013
Assignee:
Thioredoxin Systems AB
Inventors:
Arne Holmgren, Jun Lu, Alexios Vlamis-Gardikas, Rong Zhao, Karuppasamy Kandasamy, Lars Engman, Lars Engstrand, Sven Hoffner
Abstract: The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with Ki of 0.14 ?M and 0.46 ?M, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains.
Type:
Application
Filed:
March 23, 2011
Publication date:
November 24, 2011
Applicant:
THIOREDOXIN SYSTEMS AB
Inventors:
Arne Holmgren, Jun Lu, Alexios Vlamis-Gardikas, Rong Zhao, K. Kandasamy, Lars Engman, Lars Engstrand, Sven Hoffner
Abstract: The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with Ki of 0.14 ?M and 0.46 ?M, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains.
Type:
Application
Filed:
May 22, 2007
Publication date:
January 1, 2009
Applicant:
THIOREDOXIN SYSTEMS AB
Inventors:
Arne Holmgren, Jun Lu, Alexios Vlamis-Gardikas, Rong Zhao, K. Kandasamy, Lars Engman, Lars Engstrand, Sven Hoffner